Non-Invasive Biomonitoring of Pesticides

农药的非侵入式生物监测

• 批准号: 7141457
• 负责人: CHARLES TIMCHALK
• 金额: $ 44.97万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141457
• 关键词: biomedical equipment development; biosensor device; cholinesterase inhibitors; clearance rate; gas chromatography mass spectrometry; laboratory rat; method development; miniature biomedical equipment; model design /development; noninvasive diagnosis; occupational hazard; organophosphorus insecticide; pesticide biological effect; pharmacokinetics; saliva

DESCRIPTION (provided by applicant): This research project will establish a non-invasive biomonitoring capability to evaluate exposure to organophosphorus (OP) insecticides utilizing a sensitive, non-invasive, micro-analytical instrument for realtime analysis of biomarkers of exposure and response in saliva. This project will create a miniaturized nanobioelectronic biosensor that is highly selective and sensitive for the target analyte(s). In addition, a physiologically based pharmacokinetic and pharmacodynamic model (PBPK/PD) for the OP insecticide chlorpyrifos will be modified to incorporate a salivary gland compartment that will be used to quantitatively predict blood chlorpyrifos concentration and saliva cholinesterase (ChE) inhibition to estimate exposure based on a saliva specimen. The utilization of saliva for biomonitoring, coupled to real-time monitoring and modeling is a novel approach with broad application for evaluating occupational exposures to insecticides. An OP sensor will be developed based on a new biosensing principle of antigen-induced formation of nanoparticle-immuno complex nanostructure. A ChE sensor will also be developed based on the electrodetection of the ChE hydrolyzed reaction products choline and hydrogen peroxide. Subsequently, the sensors will be transformed to a "lab-on-a-chip", and the biochip performance will be characterized, optimized and validated. To validate this approach the pharmacokinetics of chlorpyrifos excretion and ChE inhibition in saliva under various physiological conditions and dose levels will be assessed to ensure that these endpoints are accurate predictors of internal dose. The development of a real-time saliva analysis coupled to a predictive pharmacokinetic model represents a significant advancement over current biomonitoring strategies. Once this model system has been adequately validated it can readily be employed to assess worker exposure to insecticides under a wide range of occupational situations.

描述（由申请人提供）：该研究项目将建立一种非侵入性的生物监测能力，以评估使用敏感，无创，微型分析仪器的有机磷（OP）杀虫剂的接触，以实时分析唾液中暴露和反应的生物标志物。该项目将创建一个微型的纳米电子生物传感器，对目标分析物具有很高的选择性和敏感性。此外，将修改基于生理的药代动力学和药效动力学模型（PBPK/PD），以纳入唾液腺室，用于定量预测基于saliva saliva saliva saliva的唾液腺室，用于定量预测血液氯磷酸盐浓度和唾液酶（CHE）的曝光。唾液对生物监测的利用，与实时监测和建模相结合，是一种新型方法，具有广泛的应用，用于评估对杀虫剂的职业暴露。 OP传感器将基于纳米颗粒 - 免疫复合纳米结构的抗原诱导形成的新生物传感原理开发。 CHE传感器还将根据CHE水解反应产物胆碱和过氧化氢的电反射开发。随后，传感器将转换为“芯片实验室”，并将对生物芯片性能进行表征，优化和验证。为了验证这种方法，在各种生理条件和剂量水平下，将评估毒死rif的药代动力学和唾液中的CHE抑制作用，以确保这些终点是内部剂量的准确预测指标。与预测药代动力学模型相连的实时唾液分析的开发代表了与当前的生物监测策略相比的重大进步。一旦该模型系统得到了充分的验证，就可以很容易地使用在广泛的职业情况下评估工人接触杀虫剂。